Microvascular disturbances during adult onset diabetes mellitus cause mild to severe impairment of peripheral vascular function in man by as yet unknown mechanisms. Previous studies indicate that adult mice treated with streptozotocin with a blood glucose concentration in excess of 300 mg%, have fewer capillaries than normal, inner arteriolar diameters are decreased and the vessel wall is thinner than normal after 8-10 weeks of hyperglycemia. The proposed study will investigate the sequence of changes in in vivo microvascular anatomy and function which lead to these changes in the severely hyperglycemic adult animal. If the sequence of events can be documented, the potential causes of the disturbances can be more logically pursued and the interrelationship of the various disturbances will be known. Adult animals treated with streptozotocin, with blood glucose concentrations in the range of 175-250 mg per cent, will be studied as a model of mild to moderate adult onset diabetes. The major objectives being whether there is a specific severity of hyperglycemia at which vascular disturbances begin and whether microvasaular disturbances in milder forms of hyperglycemia are qualitatively and quantitatively similar to those present during severe adult hyperglycemia in mice. These studies may provide an insight as to the cause of widely different severities of vascular disturbances during adult onset diabetes mellitus in man. As a part of the proposed study, streptozotocin induced diabetes in adult bats will be evaluated as a potential model to study the development of microvascular disturbances in cutaneous tissues. A specific microvascular area in the wing of the bat will be studied during health and at intervals after diabetes is established. This will allow a quantitative evaluation of the sequence of microvascular changes in the same unanesthetized mammal during the development of diabetes.